{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T06:34:29Z","timestamp":1768977269958,"version":"3.49.0"},"reference-count":120,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T00:00:00Z","timestamp":1682985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PRIN","award":["2020K53E57"],"award-info":[{"award-number":["2020K53E57"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Symmetry"],"abstract":"<jats:p>Biomolecules are frequently chiral compounds, existing in enantiomeric forms. Amino acids represent a meaningful example of chiral biological molecules. Both L- and D-amino acids play key roles in the biochemical structure and metabolic processes of living organisms, from bacteria to mammals. In this review, we explore the enantiospecific interaction between proteins and chiral amino acids, introducing theoretical models and describing the molecular basis of the ability of some of the most important enzymes involved in the metabolism of amino acids (i.e., amino acid oxidases, dehydrogenases, and aminotransferases) to discriminate the opposite enantiomers. Our analysis showcases the power of natural evolution in shaping biological processes. Accordingly, the importance of amino acids spurred nature to evolve strictly enantioselective enzymes both through divergent evolution, starting from a common ancestral protein, or through convergent evolution, starting from different scaffolds: intriguingly, the active sites of these enzymes are frequently related by a mirror symmetry.<\/jats:p>","DOI":"10.3390\/sym15051017","type":"journal-article","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T01:36:38Z","timestamp":1683077798000},"page":"1017","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Symmetric Active Site of Enantiospecific Enzymes"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8384-7992","authenticated-orcid":false,"given":"Elena","family":"Rosini","sequence":"first","affiliation":[{"name":"\u201cThe Protein Factory 2.0\u201d, Department of Biotechnology and Life Sciences (DBSV), University of Insubria, Via Dunant 3, 21100 Varese, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1733-7243","authenticated-orcid":false,"given":"Loredano","family":"Pollegioni","sequence":"additional","affiliation":[{"name":"\u201cThe Protein Factory 2.0\u201d, Department of Biotechnology and Life Sciences (DBSV), University of Insubria, Via Dunant 3, 21100 Varese, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3688-3397","authenticated-orcid":false,"given":"Gianluca","family":"Molla","sequence":"additional","affiliation":[{"name":"\u201cThe Protein Factory 2.0\u201d, Department of Biotechnology and Life Sciences (DBSV), University of Insubria, Via Dunant 3, 21100 Varese, Italy"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/nchem.2790","article-title":"Pasteur and the Art of Chirality","volume":"9","author":"Gal","year":"2017","journal-title":"Nat. Chem."},{"key":"ref_2","first-page":"422","article-title":"Recherches Sur Les Relations Qui Peuvent Exister Entre La Forme Cristalline, La Composition Chimique et Le Sens de La Polarisation Rotatoire","volume":"24","author":"Pasteur","year":"1848","journal-title":"Ann. Chim. Phys."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1002\/cber.18910240278","article-title":"\u00dcber Die Konfiguration Des Traubenzuckers Und Seiner Isomeren, I & II","volume":"24","author":"Fischer","year":"1891","journal-title":"Ber. Dtsch. Chem. Ges."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.tibs.2004.07.002","article-title":"Ancestral Lipid Biosynthesis and Early Membrane Evolution","volume":"29","author":"Moreira","year":"2004","journal-title":"Trends Biochem. Sci."},{"key":"ref_5","first-page":"29","article-title":"An Evolutionary Perspective on Amino Acids","volume":"3","author":"Romero","year":"2010","journal-title":"Nat. Educ."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1128\/AEM.02911-12","article-title":"Extensive Reduction of Cell Viability and Enhanced Matrix Production in Pseudomonas Aeruginosa PAO1 Flow Biofilms Treated with a D-Amino Acid Mixture","volume":"79","author":"Sanchez","year":"2013","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5616","DOI":"10.1128\/JB.05534-11","article-title":"Inhibitory Effects of D-Amino Acids on Staphylococcus Aureus Biofilm Development","volume":"193","author":"Hochbaum","year":"2011","journal-title":"J. Bacteriol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"5391","DOI":"10.1128\/JB.00975-13","article-title":"D-Amino Acids Indirectly Inhibit Biofilm Formation in Bacillus Subtilis by Interfering with Protein Synthesis","volume":"195","author":"Leiman","year":"2013","journal-title":"J. Bacteriol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1146\/annurev.bi.38.070169.002441","article-title":"Structure and Biosynthesis of the Bacterial Cell Wall","volume":"38","author":"Osborn","year":"1969","journal-title":"Annu. Rev. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1523\/JNEUROSCI.17-05-01604.1997","article-title":"D-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors","volume":"17","author":"Schell","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.1007\/s00018-010-0307-9","article-title":"Metabolism of the Neuromodulator D-serine","volume":"67","author":"Pollegioni","year":"2010","journal-title":"Cell Mol. Life Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1007\/s00726-014-1759-2","article-title":"Current Knowledge of D-aspartate in Glandular Tissues","volume":"46","author":"Santillo","year":"2014","journal-title":"Amino Acids"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s00253-019-10264-9","article-title":"D-Amino Acids in Foods","volume":"104","author":"Marcone","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6053","DOI":"10.1021\/ja00386a035","article-title":"O-Sulfated. Beta.-Lactam Hydroxamic Acids (Monosulfactams). Novel Monocyclic. Beta.-Lactam Antibiotics of Synthetic Origin","volume":"104","author":"Gordon","year":"1982","journal-title":"J. Am. Chem. Soc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"741","DOI":"10.3390\/biom3040741","article-title":"Biocatalytic Synthesis of Chiral Alcohols and Amino Acids for Development of Pharmaceuticals","volume":"3","author":"Patel","year":"2013","journal-title":"Biomolecules"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1097\/00001721-199601000-00009","article-title":"Effects of Inogatran, a New Low-Molecular-Weight Thrombin Inhibitor, in Rat Models of Venous and Arterial Thrombosis, Thrombolysis and Bleeding Time","volume":"7","author":"Gustafsson","year":"1996","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Pollegioni, L., Rosini, E., and Molla, G. (2020). Advances in Enzymatic Synthesis of D-Amino Acids. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093206"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Coelho, M.M., Fernandes, C., Remi\u00e3o, F., and Tiritan, M.E. (2021). Enantioselectivity in Drug Pharmacokinetics and Toxicity: Pharmacological Relevance and Analytical Methods. Molecules, 26.","DOI":"10.3390\/molecules26113113"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jpha.2015.12.004","article-title":"Significance and Challenges of Stereoselectivity Assessing Methods in Drug Metabolism","volume":"6","author":"Shen","year":"2016","journal-title":"J. Pharm. Anal."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Leek, H., and Andersson, S. (2017). Preparative Scale Resolution of Enantiomers Enables Accelerated Drug Discovery and Development. Molecules, 22.","DOI":"10.3390\/molecules22010158"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1042\/bj0271257","article-title":"Studies on the Relationship between Chemical Constitution and Physiological Action","volume":"27","author":"Easson","year":"1933","journal-title":"Biochem. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1002\/cmdc.201800761","article-title":"Chiral Graphs: Reduced Representations of Ligand Scaffolds for Stereoselective Biomolecular Recognition, Drug Design, and Enhanced Exploration of Chemical Structure Space","volume":"14","author":"Mikhael","year":"2019","journal-title":"ChemMedChem"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/35001144","article-title":"A New Model for Protein Stereospecificity","volume":"403","author":"Mesecar","year":"2000","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/0003-9861(81)90492-6","article-title":"Phenylalanine Ammonia-Lyase: Mirror-Image Packing of D- and L-Phenylalanine and D- and L-Transition State Analogs into the Active Site","volume":"211","author":"Hanson","year":"1981","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"10367","DOI":"10.1002\/chem.201905826","article-title":"Through the Looking Glass: Chiral Recognition of Substrates and Products at the Active Sites of Racemases and Epimerases","volume":"26","author":"Bearne","year":"2020","journal-title":"Chem. A Eur. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0003-9861(03)00169-3","article-title":"Diastereoisomerism, Contact Points, and Chiral Selectivity: A Four-Site Saga","volume":"414","author":"Bentley","year":"2003","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6430","DOI":"10.1021\/acscatal.0c00983","article-title":"Modeling Enzymatic Enantioselectivity using Quantum Chemical Methodology","volume":"10","author":"Sheng","year":"2020","journal-title":"ACS Catal."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00249-020-01460-x","article-title":"Chiral Discrimination in a Mutated IDH Enzymatic Reaction in Cancer: A Computational Perspective","volume":"49","author":"Thamim","year":"2020","journal-title":"Eur. Biophys. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1128\/AEM.02710-16","article-title":"Structural Insights into L-Tryptophan Dehydrogenase from a Photoautotrophic Cyanobacterium, Nostoc Punctiforme","volume":"83","author":"Wakamatsu","year":"2017","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1073\/pnas.0808269106","article-title":"Arginine Racemization by Coupled Catabolic and Anabolic Dehydrogenases","volume":"106","author":"Li","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"9323","DOI":"10.1007\/s00253-013-5230-1","article-title":"L-Amino Acid Oxidase as Biocatalyst: A Dream Too Far?","volume":"97","author":"Pollegioni","year":"2013","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1128\/JB.188.7.2493-2501.2006","article-title":"The Antimicrobial Activity of Marinocine, Synthesized by Marinomonas Mediterranea, Is Due to Hydrogen Peroxide Generated by Its Lysine Oxidase Activity","volume":"188","author":"Solano","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/j.bbapap.2006.08.014","article-title":"A Novel Type of Lysine Oxidase: L-Lysine-\u03b5-Oxidase","volume":"1764","author":"Solano","year":"2006","journal-title":"Biochim. Et Biophys. Acta (BBA) Proteins Proteom."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1093\/jxb\/ern352","article-title":"Detection of an L-Amino Acid Dehydrogenase Activity in Synechocystis Sp. PCC 6803","volume":"60","author":"Schriek","year":"2009","journal-title":"J. Exp. Bot."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1042\/bj0291951","article-title":"Metabolism of Amino-Acids","volume":"29","author":"Krebs","year":"1935","journal-title":"Biochem. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7496","DOI":"10.1073\/pnas.93.15.7496","article-title":"Crystal Structure of D-Amino Acid Oxidase: A Case of Active Site Mirror-Image Convergent Evolution with Flavocytochrome B2","volume":"93","author":"Mattevi","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1080\/10242420290020679","article-title":"D-Amino Acid Oxidase as an Industrial Biocatalyst","volume":"20","author":"Pilone","year":"2002","journal-title":"Biocatal. Biotransformation"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1046\/j.1432-1033.2002.02790.x","article-title":"Overexpression of a Recombinant Wild-Type and His-Tagged Bacillus Subtilis Glycine Oxidase in Escherichia Coli","volume":"269","author":"Job","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6985","DOI":"10.1074\/jbc.M111095200","article-title":"Glycine Oxidase from Bacillus Subtilis. Characterization of a New Flavoprotein","volume":"277","author":"Job","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"29718","DOI":"10.1074\/jbc.M401224200","article-title":"Structure-Function Correlation in Glycine Oxidase from Bacillus Subtilis","volume":"279","author":"Diederichs","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.sbi.2003.10.006","article-title":"Structural Biology of Enzymes of the Thiamin Biosynthesis Pathway","volume":"13","author":"Settembre","year":"2003","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"12463","DOI":"10.1073\/pnas.97.23.12463","article-title":"The X-Ray Structure of D-Amino Acid Oxidase at Very High Resolution Identifies the Chemical Mechanism of Flavin-Dependent Substrate Dehydrogenation","volume":"97","author":"Umhau","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1007\/s00018-007-6558-4","article-title":"Physiological Functions of D-Amino Acid Oxidases: From Yeast to Humans","volume":"64","author":"Pollegioni","year":"2007","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4204","DOI":"10.1093\/emboj\/19.16.4204","article-title":"The Structure of L-Amino Acid Oxidase Reveals the Substrate Trajectory into an Enantiomerically Conserved Active Site","volume":"19","author":"Pawelek","year":"2000","journal-title":"EMBO J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12010-012-9611-1","article-title":"Advances in Non-Snake Venom l-Amino Acid Oxidase","volume":"167","author":"Yu","year":"2012","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_46","first-page":"337","article-title":"L-Amino Acid Oxidases: Properties and Molecular Mechanisms of Action","volume":"5","author":"Lukasheva","year":"2011","journal-title":"Biochem. Mosc. Suppl. B Biomed. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"196754","DOI":"10.1155\/2014\/196754","article-title":"Snake Venom L-Amino Acid Oxidases: Trends in Pharmacology and Biochemistry","volume":"2014","author":"Izidoro","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Nielsen, V.G. (2019). Characterization of L-Amino Acid Oxidase Derived from Crotalus Adamanteus Venom: Procoagulant and Anticoagulant Activities. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194853"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4519","DOI":"10.1021\/jf104603w","article-title":"A Novel L-Amino Acid Oxidase from Trichoderma Harzianum ETS 323 Associated with Antagonism of Rhizoctonia Solani","volume":"59","author":"Yang","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5493","DOI":"10.1128\/JB.00549-08","article-title":"Hydrogen Peroxide Linked to Lysine Oxidase Activity Facilitates Biofilm Differentiation and Dispersal in Several Gram-Negative Bacteria","volume":"190","author":"Egan","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.cbpb.2007.10.013","article-title":"Antibacterial Action of L-Amino Acid Oxidase from the Skin Mucus of Rockfish Sebastes Schlegelii","volume":"149","author":"Kitani","year":"2008","journal-title":"Comp. Biochem. Physiol. B Biochem. Mol. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7847","DOI":"10.1007\/s00253-015-6844-2","article-title":"Antibacterial Properties of L-Amino Acid Oxidase: Mechanisms of Action and Perspectives for Therapeutic Applications","volume":"99","author":"Kasai","year":"2015","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Puiffe, M.-L., Lachaise, I., Molinier-Frenkel, V., and Castellano, F. (2013). Antibacterial Properties of the Mammalian L-Amino Acid Oxidase IL4I1. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054589"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"24439","DOI":"10.1074\/jbc.M110.131193","article-title":"O2 Reactivity of Flavoproteins: Dynamic Access of Dioxygen to the Active Site and Role of a H+ Relay System in D-Amino Acid Oxidase","volume":"285","author":"Saam","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.abb.2018.10.002","article-title":"Structural Determinants for Substrate Specificity of Flavoenzymes Oxidizing D-Amino Acids","volume":"660","author":"Ball","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"24715","DOI":"10.1074\/jbc.M908193199","article-title":"Role of Arginine 285 in the Active Site of Rhodotorula gracilis D-amino Acid Oxidase. A Site-Directed Mutagenesis Study","volume":"275","author":"Molla","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1002\/tcr.20129","article-title":"Human D-Amino Acid Oxidase: An Update and Review","volume":"7","author":"Kawazoe","year":"2007","journal-title":"Chem. Rec."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1038\/s41598-017-03177-y","article-title":"pH-Dependent Enantioselectivity of D-Amino Acid Oxidase in Aqueous Solution","volume":"7","author":"Liu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0022-2836(02)01062-8","article-title":"Yeast D-Amino Acid Oxidase: Structural Basis of Its Catalytic Properties","volume":"324","author":"Pollegioni","year":"2002","journal-title":"J. Mol. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1093\/jb\/mvh068","article-title":"Cloning and Expression in Escherichia Coli of the D-Aspartate Oxidase Gene from the Yeast Cryptococcus Humicola and Characterization of the Recombinant Enzyme","volume":"135","author":"Takahashi","year":"2004","journal-title":"J. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11865","DOI":"10.1016\/S0021-9258(19)49778-0","article-title":"The Primary Structure of the Flavoprotein D-Aspartate Oxidase from Beef Kidney","volume":"267","author":"Negri","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1002\/yea.1303","article-title":"Physiological Role Of D-Aspartate Oxidase in the Assimilation and Detoxification Of D-Aspartate in the Yeast Cryptococcus Humicola","volume":"22","author":"Takahashi","year":"2005","journal-title":"Yeast"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1111\/febs.14691","article-title":"Secreted D-Aspartate Oxidase Functions in C. Elegans Reproduction and Development","volume":"286","author":"Saitoh","year":"2019","journal-title":"FEBS J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1096\/fj.201901703R","article-title":"Structure and Kinetic Properties of Human D-Aspartate Oxidase, the Enzyme-Controlling d-Aspartate Levels in Brain","volume":"34","author":"Molla","year":"2020","journal-title":"FASEB J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1248\/bpb.b14-00690","article-title":"Characterization of the Enzymatic and Structural Properties of Human D-Aspartate Oxidase and Comparison with Those of the Rat and Mouse Enzymes","volume":"38","author":"Katane","year":"2015","journal-title":"Biol. Pharm. Bull."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.1007\/s00253-020-10439-9","article-title":"D-Aspartate Oxidase: Distribution, Functions, Properties, and Biotechnological Applications","volume":"104","author":"Takahashi","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1111\/j.1432-1033.1996.0427u.x","article-title":"L-Aspartate Oxidase from Escherichia Coli. II. Interaction with C4 Dicarboxylic Acids and Identification of a Novel L-Aspartate:Fumarate Oxidoreductase Activity","volume":"239","author":"Tedeschi","year":"1996","journal-title":"Eur. J. Biochem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"10457","DOI":"10.1074\/jbc.M115.703819","article-title":"Structure-Function Relationships in L-Amino Acid Deaminase, a Flavoprotein Belonging to a Novel Class of Biotechnologically Relevant Enzymes","volume":"291","author":"Motta","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2244","DOI":"10.1271\/bbb.63.2244","article-title":"Cloning of L-Amino Acid Deaminase Gene from Proteus Vulgaris","volume":"63","author":"Takahashi","year":"1999","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.biotechadv.2017.07.011","article-title":"Breaking the Mirror: L-Amino Acid Deaminase, a Novel Stereoselective Biocatalyst","volume":"35","author":"Molla","year":"2017","journal-title":"Biotechnol. Adv."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/S0039-9140(03)00177-2","article-title":"Determination of L- And D-Enantiomers of Methotrexate Using Amperometric Biosensors","volume":"60","author":"Stefan","year":"2003","journal-title":"Talanta"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/S0956-5663(03)00200-8","article-title":"Development of a L-Alanine Sensor for the Monitoring of a Fermentation Using the Improved Selectivity by the Combination of D-Amino Acid Oxidase and Pyruvate Oxidase","volume":"19","author":"Inaba","year":"2003","journal-title":"Biosens. Bioelectron."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1006\/abio.2001.5371","article-title":"Chiral Analysis of Amino Acids Using Electrochemical Composite Bienzyme Biosensors","volume":"298","author":"Serra","year":"2001","journal-title":"Anal. Biochem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.jbiotec.2008.06.001","article-title":"A Biosensor for All D-Amino Acids Using Evolved D-Amino Acid Oxidase","volume":"135","author":"Rosini","year":"2008","journal-title":"J. Biotechnol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1021\/ac702230w","article-title":"Characterization of a Yeast D-Amino Acid Oxidase Microbiosensor for D-Serine Detection in the Central Nervous System","volume":"80","author":"Pernot","year":"2008","journal-title":"Anal. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.tibtech.2011.01.010","article-title":"New Biotech Applications from Evolved D-Amino Acid Oxidases","volume":"29","author":"Pollegioni","year":"2011","journal-title":"Trends Biotechnol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5359","DOI":"10.1039\/C8CY01380B","article-title":"In Vitro Evolution of an L-Amino Acid Deaminase Active on L-1-Naphthylalanine","volume":"8","author":"Melis","year":"2018","journal-title":"Catal. Sci. Technol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/s002800050557","article-title":"L -Amino Acid Oxidase (LOX) Modulation of Melphalan Activity against Intracranial Glioma","volume":"39","author":"Moynihan","year":"1996","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_79","first-page":"1152","article-title":"L-Lysine Alpha-Oxidase: Physicochemical and Biological Properties","volume":"67","author":"Lukasheva","year":"2002","journal-title":"Biochemistry"},{"key":"ref_80","first-page":"173","article-title":"Properties and Prospects of Practical Use of Extracellular L-Glutamate Oxidase from Streptomyces Sp. Z-11-6","volume":"40","author":"Sukhacheva","year":"2004","journal-title":"Prikl. Biokhim. Mikrobiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.jmb.2007.06.017","article-title":"Convergent Evolution of Enzyme Active Sites Is Not a Rare Phenomenon","volume":"372","author":"Gherardini","year":"2007","journal-title":"J. Mol. Biol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.enzmictec.2014.04.002","article-title":"Biochemical Characterization of an L-Tryptophan Dehydrogenase from the Photoautotrophic Cyanobacterium Nostoc Punctiforme","volume":"60","author":"Ogura","year":"2014","journal-title":"Enzyme Microb. Technol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"16109","DOI":"10.1021\/bi972024x","article-title":"Determinants of Substrate Specificity in the Superfamily of Amino Acid Dehydrogenases","volume":"36","author":"Baker","year":"1997","journal-title":"Biochemistry"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1006\/jmbi.1993.1647","article-title":"Evolution of Substrate Diversity in the Superfamily of Amino Acid Dehydrogenases","volume":"234","author":"Britton","year":"1993","journal-title":"J. Mol. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1128\/AEM.70.2.937-942.2004","article-title":"Highly Stable L-Lysine 6-Dehydrogenase from the Thermophile Geobacillus Stearothermophilus Isolated from a Japanese Hot Spring: Characterization, Gene Cloning and Sequencing, and Expression","volume":"70","author":"Heydari","year":"2004","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1002\/jctb.7018","article-title":"Chiral Resolution of DL-glutamic Acid by a Chiral Additive","volume":"97","author":"Zhou","year":"2022","journal-title":"J. Chem. Technol. Biotechnol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.bbrc.2015.02.109","article-title":"Structural Insights into Domain Movement and Cofactor Specificity of Glutamate Dehydrogenase from Corynebacterium Glutamicum","volume":"459","author":"Son","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1002\/1873-3468.12667","article-title":"Crystal Structure of the 2-Iminoglutarate-Bound Complex of Glutamate Dehydrogenase from Corynebacterium Glutamicum","volume":"591","author":"Tomita","year":"2017","journal-title":"FEBS Lett."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0014-5793(83)80066-0","article-title":"Effects of Solubilisation on Some Properties of the Membrane-Bound Respiratory Enzyme D-Amino Acid Dehydrogenase of Escherichia Coli","volume":"151","author":"Jones","year":"1983","journal-title":"FEBS Lett."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4487","DOI":"10.1016\/S0021-9258(19)85517-5","article-title":"Purification and Properties of D-Amino Acid Dehydrogenase, an Inducible Membrane-Bound Iron-Sulfur Flavoenzyme from Escherichia Coli B","volume":"255","author":"Olsiewski","year":"1980","journal-title":"J. Biol. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1007\/s10529-017-2388-0","article-title":"Expression, Purification, and Characterization of a Membrane-Bound D-Amino Acid Dehydrogenase from Proteus Mirabilis JN458","volume":"39","author":"Xu","year":"2017","journal-title":"Biotechnol. Lett."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"5853","DOI":"10.1021\/bi9630570","article-title":"Active Site Plasticity in D-Amino Acid Oxidase: A Crystallographic Analysis","volume":"36","author":"Todone","year":"1997","journal-title":"Biochemistry"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1021\/acs.biochem.7b00098","article-title":"Importance of Loop L1 Dynamics for Substrate Capture and Catalysis in Pseudomonas Aeruginosa D-Arginine Dehydrogenase","volume":"56","author":"Ouedraogo","year":"2017","journal-title":"Biochemistry"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1006\/jmbi.1996.0508","article-title":"Crystal Structure of the Pyridoxal-5\u2032-Phosphate Dependent Cystathionine \u03b2-Lyase FromEscherichia Coliat 1.83 \u00c5","volume":"262","author":"Clausen","year":"1996","journal-title":"J. Mol. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Percudani, R., and Peracchi, A. (2009). The B6 Database: A Tool for the Description and Classification of Vitamin B6-Dependent Enzymatic Activities and of the Corresponding Protein Families. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-273"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3389\/fmolb.2019.00004","article-title":"Current Advances on Structure-Function Relationships of Pyridoxal 5\u2032-Phosphate-Dependent Enzymes","volume":"6","author":"Liang","year":"2019","journal-title":"Front. Mol. Biosci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1002\/pro.5560040705","article-title":"Modeling of the Spatial Structure of Eukaryotic Ornithine Decarboxylases","volume":"4","author":"Grishin","year":"1995","journal-title":"Protein Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1016\/S0969-2126(00)00085-X","article-title":"The Manifold of Vitamin B6 Dependent Enzymes","volume":"8","author":"Schneider","year":"2000","journal-title":"Structure"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3527","DOI":"10.1111\/j.1742-4658.2008.06516.x","article-title":"D-Amino Acids in the Brain: Structure and Function of Pyridoxal Phosphate-Dependent Amino Acid Racemases","volume":"275","author":"Yoshimura","year":"2008","journal-title":"FEBS J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"23900","DOI":"10.1016\/S0021-9258(18)54368-4","article-title":"The K258R Mutant of Aspartate Aminotransferase Stabilizes the Quinonoid Intermediate","volume":"266","author":"Toney","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1016\/j.bbapap.2011.05.019","article-title":"Controlling Reaction Specificity in Pyridoxal Phosphate Enzymes","volume":"1814","author":"Toney","year":"2011","journal-title":"Biochim. Biophys. Acta (BBA)-Proteins Proteom."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1007\/s00253-020-10369-6","article-title":"Structural Insight into the Substrate Specificity of PLP Fold Type IV Transaminases","volume":"104","author":"Bezsudnova","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1080\/10242420601033878","article-title":"Multistep Enzyme Catalysed Deracemisation of 2-Naphthyl Alanine","volume":"24","author":"Caligiuri","year":"2006","journal-title":"Biocatal. Biotransformation"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.biotechadv.2014.12.012","article-title":"Bioinformatic Analysis of a PLP-Dependent Enzyme Superfamily Suitable for Biocatalytic Applications","volume":"33","author":"Vickers","year":"2015","journal-title":"Biotechnol. Adv."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.watres.2016.01.037","article-title":"Inhibition of Biofilm Formation by D-Tyrosine: Effect of Bacterial Type and D-Tyrosine Concentration","volume":"92","author":"Yu","year":"2016","journal-title":"Water Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1126\/science.1188628","article-title":"D-Amino Acids Trigger Biofilm Disassembly","volume":"328","author":"Romero","year":"2010","journal-title":"Science"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1093\/jb\/mvab043","article-title":"D-Amino Acid Metabolism in Bacteria","volume":"170","author":"Miyamoto","year":"2021","journal-title":"J. Biochem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s00726-020-02830-7","article-title":"Involvement of Penicillin-Binding Proteins in the Metabolism of a Bacterial Peptidoglycan Containing a Non-Canonical D-Amino Acid","volume":"52","author":"Miyamoto","year":"2020","journal-title":"Amino Acids"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"fnw198","DOI":"10.1093\/femsle\/fnw198","article-title":"D-Phenylalanine Inhibits Biofilm Development of a Marine Microbe, Pseudoalteromonas Sp. SC2014","volume":"363","author":"Li","year":"2016","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"9021","DOI":"10.1038\/s41598-020-66082-x","article-title":"Evaluation of Anti-Biofilm Activity of Acidic Amino Acids and Synergy with Ciprofloxacin on Staphylococcus Aureus Biofilms","volume":"10","author":"Warraich","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"97957","DOI":"10.1172\/jci.insight.97957","article-title":"Gut Microbiota\u2013Derived D-Serine Protects against Acute Kidney Injury","volume":"3","author":"Nakade","year":"2018","journal-title":"JCI Insight"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"7703","DOI":"10.1126\/scisignal.aam7703","article-title":"Bacterial D-Amino Acids Suppress Sinonasal Innate Immunity through Sweet Taste Receptors in Solitary Chemosensory Cells","volume":"10","author":"Lee","year":"2017","journal-title":"Sci. Signal"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1016\/j.jaci.2016.09.003","article-title":"D-Tryptophan from Probiotic Bacteria Influences the Gut Microbiome and Allergic Airway Disease","volume":"139","author":"Kepert","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"5933","DOI":"10.1111\/febs.16452","article-title":"Identification of a Novel D-amino Acid Aminotransferase Involved in D-glutamate Biosynthetic Pathways in the Hyperthermophile Thermotoga Maritima","volume":"289","author":"Miyamoto","year":"2022","journal-title":"FEBS J."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"9661","DOI":"10.1021\/bi00030a002","article-title":"Crystal Structure of a D-Amino Acid Aminotransferase: How the Protein Controls Stereoselectivity","volume":"34","author":"Sugio","year":"1995","journal-title":"Biochemistry"},{"key":"ref_116","first-page":"79","article-title":"Stereochemical Aspects of Pyridoxal Phosphate Catalysis","volume":"35","author":"Dunathan","year":"2006","journal-title":"Adv. Enzymol. Relat. Areas Mol. Biol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/tcr.1021","article-title":"Stereospecificity for the Hydrogen Transfer of Pyridoxal Enzyme Reactions","volume":"1","author":"Soda","year":"2001","journal-title":"Chem. Rec."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1093\/protein\/7.3.405","article-title":"The Structural Basis for the Altered Substrate Specificity of the R292D Active Site Mutant of Aspartate Aminotransferase from E. coli","volume":"7","author":"Almo","year":"1994","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_119","first-page":"1572","article-title":"Properties of Bacterial and Archaeal Branched-Chain Amino Acid Aminotransferases","volume":"82","author":"Bezsudnova","year":"2017","journal-title":"Biochemistry"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3725","DOI":"10.1021\/bi026722f","article-title":"Crystal Structures of Branched-Chain Amino Acid Aminotransferase Complexed with Glutamate and Glutarate: True Reaction Intermediate and Double Substrate Recognition of the Enzyme","volume":"42","author":"Goto","year":"2003","journal-title":"Biochemistry"}],"container-title":["Symmetry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-8994\/15\/5\/1017\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:28:28Z","timestamp":1760124508000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-8994\/15\/5\/1017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,2]]},"references-count":120,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["sym15051017"],"URL":"https:\/\/doi.org\/10.3390\/sym15051017","relation":{},"ISSN":["2073-8994"],"issn-type":[{"value":"2073-8994","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,2]]}}}